Imaging depression in people with Parkinson's disease

Identifying the Neural Basis of Depression in Parkinson's Disease

This study looks at how depression affects the brains of people with Parkinson's disease and tests if a single dose of ketamine can help improve their symptoms.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 40 Years to 80 Years
• Sex: All
• Sponsor: Yale University (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT06402955 on ClinicalTrials.gov

What this trial studies

This observational study aims to identify neural substrates of depression in individuals with Parkinson's Disease aged 40 to 80 who are experiencing depressive symptoms. It will compare participants with Parkinson's and depression to those with Parkinson's without depression, individuals with Major Depressive Disorder without Parkinson's, and healthy controls. Participants will undergo PET and MRI scans, and a subset may receive a single dose of ketamine to assess its effects on synaptic density and connectivity. The study seeks to answer key questions about synaptic deficits and the potential antidepressant response to ketamine.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 40-80 with a clinical diagnosis of Parkinson's Disease and moderate depressive symptoms.

Not a fit: Patients with significant primary psychiatric disorders other than Major Depressive Disorder or those with dementia may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to targeted treatments for depression in Parkinson's Disease, improving patient outcomes.

How similar studies have performed: Other studies have shown promise in using imaging techniques to understand depression in neurological conditions, but this specific approach is novel.

Eligibility criteria

Inclusion Criteria:

1. Age 40-80.
2. For women of reproductive potential, a negative pregnancy test at screening and scanning
3. For PD patients, clinical diagnosis of PD, able to consent and tolerate PET procedures
4. For PD depression patients - at least moderate symptom severity as determined by at least 15 on the MADRS, which has shown maximum discrimination between depressed and non-depressed PD patients.
5. For dPD patients undergoing ketamine, abstinence from drugs of abuse, other than alcohol, cannabis, nicotine and caffeine for the duration of the study. Patients with substance use disorders as defined by the DSM-5 will be excluded.

Exclusion Criteria:

1. Dementia (Montreal Cognitive Assessment (MoCA) score \<21)
2. A significant primary DSM-5 psychiatric disorder except for MDD
3. A history of or current significant medical (e.g. cardiovascular, renal), or neurological (e.g. cerebrovascular, seizure, traumatic brain injury) illness other than PD that is unstable and significantly increase their risk and/or might affect the study objectives, as determined by study physicians.
4. Prior radiation exposure for research purposes within such that participation in this study would place them over FDA limits for annual radiation exposure
5. Medications affecting SV2A availability (e.g. levetiracetam)
6. For dPD patients receiving ketamine, uncontrolled hypertension, defined as average blood pressure greater than or equal to 140 mmHg or an average diastolic blood pressure greater than or equal to 90 mmHg among those patients who have hypertension.
7. Contraindications to MRI.
8. For patients undergoing arterial sampling for the PET scan: Iodine allergy, bleeding disorder and/or use of blood thinning medication
9. Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.

Where this trial is running

New Haven, Connecticut

• Yale University — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Study coordinator: Sophie Holmes

Conditions Parkinson's Disease; Major Depressive Disorder; Imaging